Safety, Tolerability and Efficacy of Ceftaroline in Paediatrics With Late-Onset Sepsis

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to study follow-up (SFU) visit (28 to 35 days after last dose of study treatment) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.

Time frame: Baseline up to SFU visit (up to a maximum study duration of 49 days)

Population: Safety analysis set consisted of all enrolled participants for whom informed consent form was signed and received any amount of ceftaroline fosamil.

Clinical response was assessed by the investigator as Cure, Failure or Indeterminate at End of treatment (EOT) and Test of Cure (TOC). Favorable clinical response was defined as clinical response of Cure (defined as resolution of all acute signs and symptoms of Late-onset sepsis \[LOS\] or improvement to such an extent that no further antibacterial therapy is required). EOT visit occurred within 24 hours after the end of last infusion. TOC visit occurred within 8 to 15 days after the last dose of study therapy.

Time frame: EOT visit (up to Day 15), TOC visit (up to Day 29)

Population: Modified ITT analysis set: participants who received ceftaroline fosamil and met minimal disease criteria of late-onset sepsis (diagnosis of sepsis within 36 hours before enrolment \[defined as presence of \>=2 clinical criteria, \>=1 laboratory criteria in presence of or as a result of suspected /proven bacterial infection that requires IV therapy\]).

Microbiological response was determining programmatically and assessed at the participants level at EOT and TOC. Microbiological response was defined as Favorable (Eradication or Presumed Eradication), Unfavorable (Persistence or Presumed Persistence) or Indeterminate (participant's clinical response is Indeterminate and no microbiological culture data is available). Eradication defined as absence of the original baseline pathogen from the source specimen; presumed eradication was defined when source specimen was not available to culture and the participant was assessed as a clinical cure (resolution of all acute signs and symptoms of LOS or improvement to such an extent that no further antibacterial therapy was required). EOT visit occurred within 24 hours after the end of last infusion. TOC visit occurred within 8 to 15 days after last dose of study drug.

Time frame: EOT visit (up to Day 15), TOC visit (up to Day 29)

Population: Modified ITT analysis set: participants who received ceftaroline fosamil and met minimal disease criteria of late-onset sepsis (diagnosis of sepsis within 36 hours before enrolment \[defined as presence of \>=2 clinical criteria, \>=1 laboratory criteria in presence of or as a result of suspected /proven bacterial infection that requires IV therapy).

Ceftaroline fosamil was the prodrug of ceftaroline. Data was not summarized and provided for individual participants only and reported in this end point for only those participants who had concentrations above LOQ at any specific time-point. LOQ was 50 ng/mL

Time frame: At EOI, 15 minutes to 2 hours, 3 to 4 hours and 5 to 7 hours after EOI

Population: PK analysis set included all participants who received a known amount of ceftaroline fosamil, were randomized to a PK sample collection schedule, and had at least 1 PK sample collected.

Data was not summarized and provided for individual participants only and reported in this end point for only those participants who had concentrations above limit of quantification (LOQ). LOQ was 50 nanogram per milliliter (ng/mL).

Time frame: At the end of infusion (EOI)

Population: Pharmacokinetic (PK) analysis set included all participants who received a known amount of ceftaroline fosamil, were randomized to a PK sample collection schedule, and had at least 1 PK sample collected.

Ceftaroline M-1 was the inactive metabolite of ceftaroline. Data was not summarized and provided for individual participants only and reported in this end point for only those participants who had concentrations above LOQ at any specific time-point. LOQ was 50 ng/mL

Time frame: At EOI, 15 minutes to 2 hours, 3 to 4 hours and 5 to 7 hours after EOI

Population: The PK analysis set will include all participants who received a known amount of ceftaroline fosamil, were randomized to a PK sample collection schedule, and had at least 1 PK sample collected.